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Low incidence of hepatitis B e antigen seroconversion in patients treated with oral nucleos(t)ides in routine practice

Authors


  • Grant support: none.
  • Authors' declaration of personal interests:

    1 Brian Lin has no financial relationship to disclose.

    2 Nghiem B. Ha has no financial relationship to disclose.

    3 Anne Liu has no financial relationship to disclose.

    4 Huy N. Trinh has served as a speaker for Vertex and Bristol-Myers Squibb, consultant for Bristol-Myers Squibb, advisory board member for Gilead Sciences Inc. and Bristol-Myers Squibb, has received funding from Gilead Sciences Inc. and Roche, and owns stocks and shares in Gilead Sciences Inc.

    5 Huy A. Nguyen has served as a speaker for Gilead Sciences Inc.

    6 Khanh K. Nguyen has no financial relationship to disclose.

    7 Aijaz Ahmed has served as a consultant for Bristol-Myers Squibb, Genentech and Gilead Sciences Inc., and on advisory committee or review panel for Bristol-Myers Squibb, Genentech and Gilead Sciences Inc., and has received grant/research support from Gilead Sciences Inc.

    8 Emmet B. Keeffe has no financial relationship to disclose.

    9 Ruel T. Garcia has received grant/research support from Bristol-Myers Squibb.

    10 Gabriel Garcia has no financial relationship to disclose.

    11 Mindie H. Nguyen has served as a consultant for Bristol-Myers Squibb and Gilead Sciences Inc., and has received grant/research support from Bristol-Myers Squibb, Gilead Sciences, Novartis Pharmaceuticals, and Roche.

Correspondence

Dr Mindie H Nguyen, Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304, USA. Email: mindiehn@stanford.edu

Abstract

Background and Aim

Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, which ranges from 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates.

Methods

We conducted a retrospective cohort study of 333 consecutive treatment-naïve HBeAg-positive patients who were treated for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversion—loss of HBeAg and antibody to HBeAg (anti-HBe) development.

Results

The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 26–52) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA < 7.5 log10 IU/mL (hazard ratio [HR] = 2.59 [1.04–6.44]), P= 0.041) and alanine transaminase (ALT) > 1.5 × upper normal limit (HR = 2.86 [1.05–7.81], P = 0.040), but not the choice of nucleos(t)ides.

Conclusions

The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels. HBeAg-positive patients should be counseled about the high possibility of the long treatment duration required to achieve recommended treatment end-points.

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